Nigral GABAergic inhibition upon mesencephalic dopaminergic cell groups in rats.

Abstract

Synaptic inhibition from the substantia nigra pars reticulata (SNr) to the mesencephalic dopaminergic neurons, which was mediated by gamma (gamma)-amino-butyric acid (GABA), was investigated in a midbrain slice preparation of Wistar rats. Whole-cell patch-clamp recordings were used to record synaptic potentials/currents from the dopaminergic neurons (n = 93) located in the retrorubral field (n = 22), the substantia nigra pars compacta (n = 47) and the ventral tegmental area (n = 24). In the presence of ionotropic glutamate receptor antagonists electrical stimulation of the SNr induced inhibitory postsynaptic potentials (IPSPs) and/or currents (IPSCs) in 83 neurons. The IPSPs/IPSCs were comprised early and late components. The early IPSPs/IPSCs were mediated by chloride currents through GABA(A) receptors. The late IPSPs/IPSCs were mediated by potassium currents through GABA(B) receptors. Both GABA(A)- and GABA(B)-IPSPs were amplified by repetitive stimuli with frequencies between 25 and 200 Hz. This frequency range covers the firing frequencies of SNr neurons in vivo. It was observed that an application of a GABA(B) receptor antagonist increased the amplitude of the GABA(A)-IPSPs. The amplification was followed by a rebound depolarization that induced transient firing of dopaminergic neurons. These properties of the IPSPs were common in all of the three dopaminergic nuclei. These results suggest that postsynaptic GABA(A)- and GABA(B)-inhibition contribute to transient and persistent alternations of the excitability of dopaminergic neurons, respectively. These postsynaptic mechanisms may be, in turn, regulated by presynaptic GABA(B)-inhibition. Nigral GABAergic input may provide the temporospatial regulation of the background excitability of mesencephalic dopaminergic systems.